99 results on '"Reginato AM"'
Search Results
2. Pan-American League of Associations for Rheumatology (PANLAR) recommendations and guidelines for musculoskeletal ultrasound training in the Americas for rheumatologists.
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Pineda C, Reginato AM, Flores V, Aliste M, Alva M, Aragón-Laínez RA, González AB, Bouffard JA, Caballero-Uribe CV, Chávez-López M, Chávez-Pérez NN, Collado P, Díaz-Coto JF, Duarte M, Filippucci E, Galarza-Maldonado C, García-Kutzbach A, Godoy FJ, González-Sevillano E, and Da Silveira IG
- Published
- 2010
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3. Genetics and experimental models of crystal-induced arthritis. Lessons learned from mice and men: is it crystal clear?
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Reginato AM and Olsen BR
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- 2007
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4. Pregnancy Outcomes from a Multidisciplinary Obstetric-Medicine/Rheumatology Clinic in the United States: A Five-Year Retrospective Analysis.
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Reed G, Deeb M, Mathew J, Rigby K, Cravens E, Raker C, Jafari-Esfahani S, Reginato AM, Tarabulsi G, and Cunha JS
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Objectives: At Women & Infants Hospital in Providence, Rhode Island, the Specialty Care in Pregnancy clinic combines obstetric-medicine internists with rheumatologists to care for pregnant women with rheumatologic conditions. These clinics are scarce, with only three known similar clinics in the United States. This study aims to characterize the population cared for in this clinic, identify interventions, and analyze pregnancy outcomes for the mothers and newborns., Methods: A five-year retrospective chart review was performed from January 1
st , 2016, through December 31st , 2021., Results: Of 81 patients, 62% had a clinically diagnosed rheumatic disorder. Of 87 patient visits, which included preconception, prenatal and postpartum encounters, 54% were on conventional synthetic disease modifying antirheumatic drugs and 17% were on biologic disease modifying antirheumatic drugs. New medications were started in 52% of patients. 52% of pregnancies resulted in live births with 2% resulting in miscarriages. Prematurity occurred in 19% of newborns, and 9% had intrauterine growth restriction., Conclusion: Our study illustrates the benefits of multidisciplinary care in patients with rheumatologic disorders during their prenatal and perinatal periods. The expertise from both the obstetric-medicine internists and rheumatologists was critical in making complex decisions that weigh the benefits of therapy against potential risks for the fetus. Our multidisciplinary approach resulted in doubling of the number of patients on disease modifying therapy and increased prophylaxis with hydroxychloroquine and/or aspirin therapy as recommended by current guidelines. Additional multidisciplinary clinics of this type would help coordinate care between physicians that frequently treat these high-risk, unique patients and open the door for more research of this understudied population., (This article is protected by copyright. All rights reserved.)- Published
- 2024
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5. Systemic sclerosis is associated with increased in-patient mortality in patients hospitalized for heart failure.
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Sherif AA, Gilvaz VJ, Abraham S, Saji AM, Mathew D, Isath A, Rajendran A, Contreras J, Lanier GM, and Reginato AM
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- Humans, Female, Male, Aged, United States epidemiology, Middle Aged, Retrospective Studies, Risk Factors, Inpatients statistics & numerical data, Survival Rate trends, Length of Stay statistics & numerical data, Comorbidity, Heart Failure mortality, Heart Failure complications, Heart Failure epidemiology, Hospital Mortality trends, Scleroderma, Systemic complications, Scleroderma, Systemic mortality, Hospitalization statistics & numerical data, Hospitalization economics
- Abstract
Aims: We aimed to analyse the characteristics and in-hospital outcomes of patients hospitalized for heart failure (HF) with co-morbid systemic sclerosis (SSc) and compare them to those without SSc, using data from the National Inpatient Sample from years 2016 to 2019., Methods and Results: International Classification of Diseases, Tenth Revision diagnosis codes were used to identify hospitalized patients with a primary diagnosis of HF and secondary diagnoses of SSc from the National Inpatient Sample database from 2016 to 2019. Patients were divided into two groups: those with and without a secondary diagnosis of SSc. Baseline characteristics including demographics and co-morbidities, outcomes of mortality, length of stay (LOS), and costs were compared between the two groups. Multivariable logistic regression analysis was performed to adjust for confounders and assess the impact of SSc on in-hospital mortality, cost, and LOS. A total of 4 709 724 hospitalizations for HF were identified, with 8150 (0.17%) having a secondary diagnosis of SSc. These patients were predominantly female (82.3% vs. 47.8%; P = 0.01), younger (mean age of 67.4 vs. 71.4; P < 0.01), and had significantly lower rates of traditional cardiovascular risk factors such as coronary artery disease (35.8% vs. 50.6%; P < 0.01), hyperlipidaemia (39.1% vs. 52.9%; P < 0.01), diabetes (22.5% vs. 49.1%; P < 0.01), obesity (13.2% vs. 25.0%; P < 0.01), and hypertension (20.2% vs. 23.8%; P < 0.01). Higher rates of co-morbid pulmonary disease in the form of interstitial lung disease (23.1% vs. 2.0%; P < 0.01) and pulmonary hypertension (36.6% vs. 12.7%; P < 0.01) were noted in the SSc cohort. Unadjusted in-hospital mortality was significantly higher in the HF with SSc group [5.1% vs. 2.6%; odds ratio: 1.99; 95% confidence interval (CI): 1.60-2.48; P < 0.001]. Unadjusted mortality was also higher among female (86.7% vs. 47.0%; P < 0.01), Black (15.7% vs. 13.0%; P < 0.01), and Hispanic (13.3% vs. 6.9%; P < 0.01) patients in the SSc cohort. After adjusting for potential confounders, SSc remained independently associated with higher in-hospital mortality (adjusted odds ratio: 1.81; 95% CI: 1.44-2.28; P < 0.001). Patients with HF and SSc also had longer LOS (6.4 vs. 5.4; adjusted mean difference [AMD]: 0.37, 95% CI: 0.05-0.68; P = 0.02) and higher hospitalization costs ($67 363 vs. $57 128; AMD: 198.9; 95% CI: -4780 to 5178; P = 0.93)., Conclusions: In patients hospitalized for HF, those with SSc were noted to have higher odds of in-hospital mortality than those without SSc. Patients with HF and SSc were more likely to be younger, female, and have higher rates of co-morbid interstitial lung disease and pulmonary hypertension at baseline with fewer traditional cardiovascular risk factors., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
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- 2024
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6. A case-control study: epigenetic age acceleration in psoriasis.
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Macit B, Ragi SD, Moseley I, Molino J, McGeary JE, Horvath S, Qureshi A, Reginato AM, and Cho E
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- Humans, Case-Control Studies, Female, Male, Middle Aged, Adult, Aged, Aging genetics, Arthritis, Psoriatic genetics, DNA Methylation, Epigenesis, Genetic, Psoriasis genetics
- Abstract
Psoriasis (PsO) is a chronic inflammatory skin condition, often accompanied by psoriatic arthritis (PsA) and linked to various comorbidities and increased mortality rates. This study aimed to explore the relationship between PsO and accelerated biological aging, specifically focusing on epigenetic DNA methylation clocks. Using a matched case-control design, 20 PsO cases were selected along with age, race, and sex-matched 20 controls without PsO from the Skin Disease Biorepository at Brown Dermatology, Inc, Providence, Rhode Island. Blood samples retrieved from both groups were analyzed for DNA methylation, and epigenetic ages were calculated using DNA methylation clocks, including Horvath, Hannum, Pheno, SkinBlood, and Grim ages. Generalized estimation equations were employed to test the differences in epigenetic and chronological ages between PsO cases and controls, as well as within various subgroups in comparison to their respective controls. There were no statistically significant differences in epigenetic ages between PsO cases and controls. However, notably, PsO cases with PsA demonstrated an accelerated PhenoAge, compared to their matched controls. This study represents a pioneering investigation into the potential link between PsO and epigenetic aging, shedding light on the possibility of accelerated epigenetic aging in PsA, possibly associated with heightened inflammatory burden. These findings emphasize the systemic impact of PsA on the aging process, prompting the need for deeper exploration into autoimmune pathways, inflammation, and epigenetic modifications underlying PsO pathogenesis and aging mechanisms. Larger-scale studies with diverse populations are imperative to discern PsO subgroups experiencing accelerated biological aging and decipher the intricate interplay between PsO, inflammation, and aging pathways., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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7. Cerebral toxoplasmosis in a patient with systemic sclerosis under thalidomide treatment: A case report.
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Macit B, Arora A, Reginato AM, and Qureshi AA
- Abstract
Competing Interests: Dr Abrar A. Qureshi is a consultant for OM1 and Incyte. Dr Betul Macit reported receiving grant from European Academy of Dermatology and Venereology Society outside the submitted work. Aakash Arora has no conflicts of interests to declare.
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- 2024
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8. Walter Bauer, Marian Wilkins Ropes, and the Massachusetts General Hospital.
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Reginato AM, Petri MA, and Kay J
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- United States, Humans, Female, Hospitals, General, Massachusetts, Rheumatic Diseases, Rheumatology
- Abstract
Walter Bauer was instrumental in the development of rheumatology as a medical subspecialty, promoting careful clinical observation and description and bringing basic scientists and clinicians together to study the "anatomy, chemical composition, and metabolism of connective tissue" in the laboratory. Marian Wilkins Ropes was a pioneering woman in medicine: the first female medical resident at the Massachusetts General Hospital, the first woman appointed as an assistant professor of clinical medicine at Harvard Medical School, the first woman elected to membership in the American Society of Clinical Investigation, and the first woman elected president of the American Rheumatism Association., Competing Interests: Conflicts of interest The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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9. Rolling on the spikes.
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Li ZY and Reginato AM
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- 2024
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10. Boosting Awareness of Sclerotic Skin Diseases: Exploring the Inflammatory Overlap of Sclerotic Skin Disease and COVID-19 Vaccination.
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Anstett S, Reginato AM, Elco C, Qureshi AA, and Maher L
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- Humans, COVID-19 Vaccines, Vaccination, COVID-19 prevention & control, Skin Diseases diagnosis
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- 2024
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11. Artificial intelligence in rheumatoid arthritis: potential applications and future implications.
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Gilvaz VJ and Reginato AM
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The widespread adoption of digital health records, coupled with the rise of advanced diagnostic testing, has resulted in an explosion of patient data, comparable in scope to genomic datasets. This vast information repository offers significant potential for improving patient outcomes and decision-making, provided one can extract meaningful insights from it. This is where artificial intelligence (AI) tools like machine learning (ML) and deep learning come into play, helping us leverage these enormous datasets to predict outcomes and make informed decisions. AI models can be trained to analyze and interpret patient data, including physician notes, laboratory testing, and imaging, to aid in the management of patients with rheumatic diseases. As one of the most common autoimmune diseases, rheumatoid arthritis (RA) has attracted considerable attention, particularly concerning the evolution of diagnostic techniques and therapeutic interventions. Our aim is to underscore those areas where AI, according to recent research, demonstrates promising potential to enhance the management of patients with RA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gilvaz and Reginato.)
- Published
- 2023
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12. Bilateral Achilles Tendinopathy and Rupture With Fluoroquinolone Use.
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Cunha JS and Reginato AM
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- Humans, Fluoroquinolones adverse effects, Anti-Bacterial Agents adverse effects, Rupture, Achilles Tendon, Tendinopathy chemically induced, Tendinopathy diagnosis, Musculoskeletal Diseases
- Abstract
Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
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13. Development and validation of an OMERACT ultrasound scoring system for the extent of calcium pyrophosphate crystal deposition at the joint level and patient level.
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Sirotti S, Terslev L, Filippucci E, Iagnocco A, Moller I, Naredo E, Vreju FA, Adinolfi A, Becce F, Hammer HB, Cazenave T, Cipolletta E, Christiansen SN, Delle Sedie A, Diaz M, Figus F, Mandl P, MacCarter D, Mortada MA, Mouterde G, Porta F, Reginato AM, Schmidt WA, Serban T, Wakefield RJ, Zufferey P, Sarzi-Puttini P, Zanetti A, Damiani A, Pineda C, Keen HI, D'Agostino MA, and Filippou G
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- Humans, Female, Male, Reproducibility of Results, Diphosphates, Ultrasonography, Calcium Pyrophosphate, Calcinosis
- Abstract
Background: The Calcium Pyrophosphate Deposition (CPPD) subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound working group was established to validate ultrasound as an outcome measure instrument for CPPD, and in 2017 has developed and validated standardised definitions for elementary lesions for the detection of calcium pyrophosphate crystals in joints. The aim of this study was to develop and evaluate the reliability of a consensus-based ultrasound scoring system for CPPD extent, representing the next phase in the OMERACT methodology., Methods: In this study the novel scoring system for CPPD was developed through a stepwise process, following an established OMERACT ultrasound methodology. Following a previous systematic review to gather available evidence on existing scoring systems for CPPD, the novel scoring system was developed through a Delphi survey based on the expert opinion of the members of the OMERACT Ultrasound working group-CPPD subgroup. The reliability of the scoring system was then tested on a web-based and patient-based exercise. Intra-reader and inter-reader reliability of the new scoring system was assessed using weighted Light's κ coefficients., Findings: The four-grade semiquantitative scoring system consisted of: grade 0 (no findings consistent with CPPD), grade 1 (≤3 single spots or 1 small deposit), grade 2 (>3 single spots or >1 small deposit or ≥1 larger deposit occupying ≤50% of the structure under examination in the reference image-ie, the scanning view with the highest grade of depositions), and grade 3 (deposits that occupy more than 50% of the structure under examination in the reference image). The score should be applied to the knee (menisci and hyaline cartilage) and the triangular fibrocartilage complex of the wrist. The intra-reader and inter-reader reliabilities on static images were almost perfect (κ 0·90 [95% CI 0·79-1·00] and κ 0·84 [0·79-0·88]), and on the eight patients recruited (four [50%] female and four [50%] male) were substantial (κ 0·72 [95% CI 0·47 to 0·96] and 0·66 [0·61 to 0·71])., Interpretation: This OMERACT ultrasound scoring system for CPPD was reliable on both static images and patients. The scoring system might be a valuable tool for ensuring valid and comparable results in clinical trials and could help monitor the extent of crystal deposition in patients with CPPD in clinical practice., Funding: The Italian Ministry of Health - Ricerca Corrente., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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14. The burden of osteoarthritis: Is it a rising problem?
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Scheuing WJ, Reginato AM, Deeb M, and Acer Kasman S
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- Humans, Pandemics, Cost of Illness, Risk Factors, Knee Joint, Osteoarthritis, Hip epidemiology, Osteoarthritis, Knee
- Abstract
The objective of this review is to provide an overview of the current status of osteoarthritis (OA) as one of the most common joint disorders worldwide. Despite being the 11th cause of disability globally, there has been an increase in the prevalence, annual incidence, and years lived with disability of OA, particularly in developed and developing countries. Erosive hand OA, which affects approximately 10% of the general population, has been associated with a higher clinical burden compared to non-erosive hand OA. Patients with knee and hip OA, but not hand OA, are also at an increased risk of cardiovascular disease and all-cause mortality. Furthermore, OA has a significant contribution to healthcare costs in most countries. The recent COVID-19 pandemic has further exacerbated the disease burden of OA patients due to limited access to medical and surgical treatment. With increasing life expectancy and the aging of the global population, the burden of OA is expected to worsen. Therefore, this review highlights the importance of improving population and policymaker awareness of risk factors, such as obesity and injury, as well as early intervention and management of OA to control the future burden of the disease., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
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15. Immune-mediated diseases and subsequent risk of alopecia areata in a prospective study of US women.
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Moseley IH, Thompson JM, George EA, Ragi SD, Kang JH, Reginato AM, Qureshi A, and Cho E
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- Humans, Female, Prospective Studies, Risk Factors, Alopecia Areata epidemiology, Graves Disease
- Abstract
Introduction: Alopecia areata (AA) is the most common form of immune-mediated hair loss. Studies have begun to establish the most frequent comorbid diseases of AA; however, results have been inconsistent with few prospective studies., Methods: A total of 63,692 women in the Nurses' Health Study, 53-80 years, were prospectively followed from 2002 to 2014 to determine whether history of immune-mediated disease was associated with AA risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) for AA in relation to immune-mediated conditions were computed using Cox proportional hazard models, adjusted for AA risk factors., Results: 133 AA cases were identified during follow-up. Personal history of any immune-mediated disease was associated with increased AA risk (HR 1.72, 95% CI 1.24-2.37). History of systemic lupus erythematosus (HR 5.43, 95% CI 2.11-13.97), multiple sclerosis (HR 4.10, 95% CI 1.40-11.96), vitiligo (HR 3.13, 95% CI 1.08-9.10), psoriasis (HR 2.01, 95% CI 1.00-4.03), hypothyroidism (HR 1.88, 95% CI 1.30-2.71), and rheumatoid arthritis (HR 1.66, 95% CI 1.09-2.52) were associated with increased AA risk. History of inflammatory bowel disease or Graves' disease/hyperthyroidism was not significantly associated with AA risk., Conclusions: In this prospective study, personal history of immune-mediated diseases either individually or overall was associated with increased AA risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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16. Targeting RUNX1 as a novel treatment modality for pulmonary arterial hypertension.
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Jeong EM, Pereira M, So EY, Wu KQ, Del Tatto M, Wen S, Dooner MS, Dubielecka PM, Reginato AM, Ventetuolo CE, Quesenberry PJ, Klinger JR, and Liang OD
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- Rats, Mice, Animals, Core Binding Factor Alpha 2 Subunit genetics, Familial Primary Pulmonary Hypertension, Hypoxia complications, Pulmonary Artery, Disease Models, Animal, Pulmonary Arterial Hypertension, Hypertension, Pulmonary chemically induced, Hypertension, Pulmonary drug therapy, Hypertension, Pulmonary genetics
- Abstract
Aims: Pulmonary arterial hypertension (PAH) is a fatal disease without a cure. Previously, we found that transcription factor RUNX1-dependent haematopoietic transformation of endothelial progenitor cells may contribute to the pathogenesis of PAH. However, the therapeutic potential of RUNX1 inhibition to reverse established PAH remains unknown. In the current study, we aimed to determine whether RUNX1 inhibition was sufficient to reverse Sugen/hypoxia (SuHx)-induced pulmonary hypertension (PH) in rats. We also aimed to demonstrate possible mechanisms involved., Methods and Results: We administered a small molecule specific RUNX1 inhibitor Ro5-3335 before, during, and after the development of SuHx-PH in rats to investigate its therapeutic potential. We quantified lung macrophage recruitment and activation in vivo and in vitro in the presence or absence of the RUNX1 inhibitor. We generated conditional VE-cadherin-CreERT2; ZsGreen mice for labelling adult endothelium and lineage tracing in the SuHx-PH model. We also generated conditional Cdh5-CreERT2; Runx1(flox/flox) mice to delete Runx1 gene in adult endothelium and LysM-Cre; Runx1(flox/flox) mice to delete Runx1 gene in cells of myeloid lineage, and then subjected these mice to SuHx-PH induction. RUNX1 inhibition in vivo effectively prevented the development, blocked the progression, and reversed established SuHx-induced PH in rats. RUNX1 inhibition significantly dampened lung macrophage recruitment and activation. Furthermore, lineage tracing with the inducible VE-cadherin-CreERT2; ZsGreen mice demonstrated that a RUNX1-dependent endothelial to haematopoietic transformation occurred during the development of SuHx-PH. Finally, tissue-specific deletion of Runx1 gene either in adult endothelium or in cells of myeloid lineage prevented the mice from developing SuHx-PH, suggesting that RUNX1 is required for the development of PH., Conclusion: By blocking RUNX1-dependent endothelial to haematopoietic transformation and pulmonary macrophage recruitment and activation, targeting RUNX1 may be as a novel treatment modality for pulmonary arterial hypertension., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2022
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17. Identifying Potential Classification Criteria for Calcium Pyrophosphate Deposition Disease: Item Generation and Item Reduction.
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Tedeschi SK, Pascart T, Latourte A, Godsave C, Kundakci B, Naden RP, Taylor WJ, Dalbeth N, Neogi T, Perez-Ruiz F, Rosenthal A, Becce F, Pascual E, Andres M, Bardin T, Doherty M, Ea HK, Filippou G, FitzGerald J, Guitierrez M, Iagnocco A, Jansen TL, Kohler MJ, Lioté F, Matza M, McCarthy GM, Ramonda R, Reginato AM, Richette P, Singh JA, Sivera F, So A, Stamp LK, Yinh J, Yokose C, Terkeltaub R, Choi H, and Abhishek A
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- Calcium Pyrophosphate, Humans, Knee Joint, Wrist Joint, Chondrocalcinosis diagnosis, Crystal Arthropathies
- Abstract
Objective: Classification criteria for calcium pyrophosphate deposition (CPPD) disease will facilitate clinical research on this common crystalline arthritis. Our objective was to report on the first 2 phases of a 4-phase process for developing CPPD classification criteria., Methods: CPPD classification criteria development is overseen by a 12-member steering committee. Item generation (phase I) included a scoping literature review of 5 literature databases and contributions from a 35-member combined expert committee and 2 patient research partners. Item reduction and refinement (phase II) involved a combined expert committee meeting, discussions among clinical, imaging, and laboratory advisory groups, and an item-rating exercise to assess the influence of individual items toward classification. The steering committee reviewed the modal rating score for each item (range -3 [strongly pushes away from CPPD] to +3 [strongly pushes toward CPPD]) to determine items to retain for future phases of criteria development., Results: Item generation yielded 420 items (312 from the literature, 108 from experts/patients). The advisory groups eliminated items that they agreed were unlikely to distinguish between CPPD and other forms of arthritis, yielding 127 items for the item-rating exercise. Fifty-six items, most of which had a modal rating of +/- 2 or 3, were retained for future phases. As numerous imaging items were rated +3, the steering committee recommended focusing on imaging of the knee and wrist and 1 additional affected joint for calcification suggestive of CPP crystal deposition., Conclusion: A data- and expert-driven process is underway to develop CPPD classification criteria. Candidate items comprise clinical, imaging, and laboratory features., (© 2021 American College of Rheumatology.)
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- 2022
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18. Evolving Chest Pain in a Young Male Patient.
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White M, Reginato AM, and Cunha JS
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- Humans, Male, Chest Pain diagnosis, Chest Pain etiology, Electrocardiography
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- 2022
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19. Update of the current role of ultrasound in asymptomatic hyperuricemia. A systematic literature review.
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Gutierrez M, Sandoval H, Bertolazzi C, Soto-Fajardo C, Tellez-Gastelum RM, Reginato AM, and Clavijo-Cornejo D
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- Humans, Ultrasonography methods, Uric Acid, Arthritis, Gouty, Gout diagnostic imaging, Hyperuricemia diagnostic imaging
- Abstract
Ultrasound (US) is a recognized imaging modality for the assessment of gout. Recently it is being explored for its potential role in the evaluation of subjects with asymptomatic hyperuricemia (AH). Preliminary reports demonstrated the presence of monosodium urate (MSU)-crystal deposits including aggregates, double contour sign and/or tophi in both intra-articular and periarticular tissues of AH individuals. Although these results are exciting, the value and potential application of US in AH remain to be clearly delineated. In this systematic literature review, we aim to summarise the recent publications regarding the role of US in the assessment of AH. We analyzed possible application of US in the daily clinical practice and its future clinical and research potential in the evaluation of AH individuals., (Copyright © 2021 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
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20. Inhibition of lipid phosphatase SHIP1 expands myeloid-derived suppressor cells and attenuates rheumatoid arthritis in mice.
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So EY, Sun C, Wu KQ, Dubielecka PM, Reginato AM, and Liang OD
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- Adoptive Transfer, Animals, Arthritis, Experimental genetics, Arthritis, Experimental immunology, Arthritis, Experimental pathology, Arthritis, Rheumatoid genetics, Arthritis, Rheumatoid immunology, Arthritis, Rheumatoid pathology, Cell Communication, Cell Differentiation drug effects, Cell Proliferation drug effects, Gene Expression, Humans, Joint Capsule drug effects, Joint Capsule immunology, Joint Capsule pathology, Mice, Mice, Inbred DBA, Mice, Knockout, Myeloid-Derived Suppressor Cells cytology, Myeloid-Derived Suppressor Cells transplantation, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases antagonists & inhibitors, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases immunology, Severity of Illness Index, T-Lymphocytes, Regulatory drug effects, T-Lymphocytes, Regulatory pathology, Anti-Inflammatory Agents pharmacology, Arthritis, Experimental drug therapy, Cholestanes pharmacology, Myeloid-Derived Suppressor Cells immunology, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases genetics, T-Lymphocytes, Regulatory immunology
- Abstract
Rheumatoid arthritis (RA) is a debilitating autoimmune disease of unknown cause, characterized by infiltration and accumulation of activated immune cells in the synovial joints where cartilage and bone destructions occur. Myeloid-derived suppressor cells (MDSCs) are of myeloid origin and are able to suppress T cell responses. Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was shown to be involved in the regulation of MDSC differentiation. The purpose of the present study was to investigate the effect of inhibition of SHIP1 on the expansion of MDSCs in RA using a collagen-induced inflammatory arthritis (CIA) mouse model. In DBA/1 mice, treatment with a small molecule-specific SHIP1 inhibitor 3α-aminocholestane (3AC) induced a marked expansion of MDSCs in vivo. Both pretreatment with 3AC of DBA/1 mice prior to CIA induction and intervention with 3AC during CIA progression significantly reduced disease incidence and severity. Adoptive transfer of MDSCs isolated from 3AC-treated mice, but not naïve MDSCs from normal mice, into CIA mice significantly reduced disease incidence and severity, indicating that the 3AC-induced MDSCs were the cellular mediators of the observed amelioration of the disease. In conclusion, inhibition of SHIP1 expands MDSCs in vivo and attenuates development of CIA in mice. Small molecule-specific inhibition of SHIP1 may therefore offer therapeutic benefit to patients with RA and other autoimmune diseases.
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- 2021
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21. Sexual dimorphism in aging hematopoiesis: an earlier decline of hematopoietic stem and progenitor cells in male than female mice.
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So EY, Jeong EM, Wu KQ, Dubielecka PM, Reginato AM, Quesenberry PJ, and Liang OD
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- Animals, Antigens, Ly metabolism, Bone Marrow, Bone Marrow Transplantation, Cell Lineage, Estrogen Receptor alpha genetics, Estrogen Receptor alpha metabolism, Estrogen Receptor beta genetics, Estrogen Receptor beta metabolism, Female, Follicle Stimulating Hormone metabolism, Gene Expression, Gene Expression Regulation, Developmental, Hematopoiesis physiology, Male, Membrane Proteins metabolism, Mice, Proto-Oncogene Proteins c-kit metabolism, Receptors, Androgen genetics, Receptors, Androgen metabolism, Receptors, LH genetics, Receptors, LH metabolism, Receptors, Progesterone genetics, Receptors, Progesterone metabolism, Receptors, Prolactin genetics, Receptors, Prolactin metabolism, Stem Cell Niche, Aging physiology, Follicle Stimulating Hormone genetics, Hematopoiesis genetics, Hematopoietic Stem Cells metabolism, Receptors, FSH metabolism, Sex Characteristics
- Abstract
Adult hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) ensuring homeostasis of blood production and immune response throughout life. Sex differences in immunocompetence and mortality are well-documented in humans. However, whether HSPCs behave dimorphically between sexes during aging remains unknown. Here, we show that a significant expansion of BM-derived HSPCs occurs in the middle age of female but in the old age of male mice. We then show that a decline of HSPCs in male mice, as indicated by the expression levels of select hematopoietic genes, occurs much earlier in the aging process than that in female mice. Sex-mismatched heterochronic BM transplantations indicate that the middle-aged female BM microenvironment plays a pivotal role in sustaining hematopoietic gene expression during aging. Furthermore, a higher concentration of the pituitary sex hormone follicle-stimulating hormone (FSH) in the serum and a concomitant higher expression of its receptor on HSPCs in the middle-aged and old female mice than age-matched male mice, suggests that FSH may contribute to the sexual dimorphism in aging hematopoiesis. Our study reveals that HSPCs in the BM niches are possibly regulated in a sex-specific manner and influenced differently by sex hormones during aging hematopoiesis.
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- 2020
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22. Impact of Enthesitis on Psoriatic Arthritis Patient-Reported Outcomes and Physician Satisfaction with Treatment: Data from a Multinational Patient and Physician Survey.
- Author
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Orbai AM, Birt JA, Holdsworth EA, Booth N, Malatestinic WN, Sprabery AT, and Reginato AM
- Abstract
Introduction: Enthesitis is a core outcome domain assessed in psoriatic arthritis (PsA) clinical trials. Limited evidence describes the impact of enthesitis on patient-reported outcomes (PROs) and physician satisfaction with current treatment options. The objective of this analysis is to characterize the impact of enthesitis on PROs and physician satisfaction with currently available treatment in clinical practice settings., Methods: Cross-sectional survey of rheumatologists, dermatologists, and their consulting patients with PsA in Australia, Canada, European Union (EU5), and the USA conducted in 2018. Physicians assessed current presence and severity of enthesitis, overall disease severity, other symptoms experienced, and their satisfaction with the current treatment. PsA participant self-reported data included current pain level, EQ5D, Psoriatic Arthritis Impact of Disease (PsAID12), Health Assessment Questionnaire Disability Index (HAQ-DI), and Work Productivity and Activity Impairment Index (WPAI-SHP). Bivariate descriptive analyses were conducted to describe features and outcomes in participants with and without enthesitis., Results: Rheumatologists (454) and dermatologists (238) provided information for 3157 participants with PsA. Mean participant age was 49.2 years, and 45.9% were female. Enthesitis was present currently in 6.5% (205) of participants with PsA. Those with enthesitis had worse overall disease severity compared to those without enthesitis (12.2% vs 2.2% severe) and had more extraarticular manifestations, including nail psoriasis, dactylitis, and sacroiliitis. Enthesitis was associated with more pain, worse quality of life (QoL), increased disability, and a negative impact on work. Participants with enthesitis had higher NSAIDs and opioid pain medication use but similar biologic use. Physicians were significantly less satisfied with current PsA treatment in participants with enthesitis versus without enthesitis., Conclusions: Participants with psoriatic arthritis with enthesitis experienced significantly higher disease burden than those without enthesitis but were not more likely to receive advanced therapies. Physicians were significantly more dissatisfied with treatment in patients with enthesitis than in those without it.
- Published
- 2020
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23. Imaging of crystalline arthropathy in 2020.
- Author
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Filippucci E, Reginato AM, and Thiele RG
- Subjects
- Calcium Pyrophosphate, Humans, Tomography, X-Ray Computed, Ultrasonography, Chondrocalcinosis diagnostic imaging, Crystal Arthropathies diagnostic imaging, Gout diagnostic imaging
- Abstract
Crystal-related arthropathies are the result of crystal deposition in joint and periarticular soft tissues. Identification of urate crystals is mandatory to distinguish gout from other crystalline arthropathies, including calcium pyrophosphate dihydrate and basic calcium phosphate crystal deposition diseases. ACR/EULAR classification criteria for gout included dual-energy computed tomography and ultrasound with equal impact to the final score. Different diagnostic strengths of these imaging modalities depend on disease duration and scanned anatomic site. While ultrasound has been indicated as the first-choice imaging technique, especially in the early stages of the disease, dual-energy computed tomography has shown to be highly specific, allowing the detection of crystal deposits in anatomic sites not accessible by ultrasound, such as the spine. At the spinal level, MRI findings are usually nonspecific. Finally, there is preliminary evidence that at the knee, dual-energy computed tomography may discriminate calcium pyrophosphate dihydrate from basic calcium phosphate crystal deposits., Competing Interests: Declaration of competing interest EF has received speaking fees from AbbVie, Bristol-Myers Squibb, Novartis, Pfizer, Roche and Union Chimique Belge Pharma. AMR and RGT declare that they have no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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24. Reply.
- Author
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Dalal DS, Mbuyi N, and Reginato AM
- Subjects
- Emergency Service, Hospital, Humans, Gout, Patient Discharge
- Published
- 2020
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25. Gout Is Associated With Increased Coronary Artery Calcification and Adverse Cardiovascular Outcomes.
- Author
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Christensen JL, Yu W, Tan S, Chu A, Vargas F, Assali M, Shah NR, Reginato AM, Wu WC, Choudhary G, and Morrison AR
- Subjects
- Aged, Aged, 80 and over, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease mortality, Coronary Artery Disease therapy, Female, Gout diagnosis, Humans, Male, Middle Aged, Multidetector Computed Tomography, Progression-Free Survival, Retrospective Studies, Risk Assessment, Risk Factors, Smokers, Smoking adverse effects, Smoking epidemiology, United States epidemiology, Vascular Calcification diagnostic imaging, Vascular Calcification mortality, Vascular Calcification therapy, Veterans Health, Coronary Artery Disease epidemiology, Gout epidemiology, Vascular Calcification epidemiology
- Published
- 2020
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26. Lipid phosphatase SHIP-1 regulates chondrocyte hypertrophy and skeletal development.
- Author
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So EY, Sun C, Wu KQ, Driesman A, Leggett S, Isaac M, Spangler T, Dubielecka-Szczerba PM, Reginato AM, and Liang OD
- Subjects
- Animals, Bone and Bones metabolism, Cell Cycle physiology, Cell Proliferation physiology, Chondrogenesis genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Lipids, Mice, Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases deficiency, Cell Differentiation physiology, Chondrocytes cytology, Hypertrophy metabolism, Lipid Metabolism physiology, Osteogenesis genetics, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases metabolism, Skeleton growth & development
- Abstract
SH2-containing inositol-5'-phosphatase-1 (SHIP-1) controls the phosphatidylinositol-3'-kinase (PI3K) initiated signaling pathway by limiting cell membrane recruitment and activation of Akt. Despite the fact that many of the growth factors important to cartilage development and functions are able to activate the PI3K signal transduction pathway, little is known about the role of PI3K signaling in chondrocyte biology and its contribution to mammalian skeletogenesis. Here, we report that the lipid phosphatase SHIP-1 regulates chondrocyte hypertrophy and skeletal development through its expression in osteochondroprogenitor cells. Global SHIP-1 knockout led to accelerated chondrocyte hypertrophy and premature formation of the secondary ossification center in the bones of postnatal mice. Drastically higher vascularization and greater number of c-kit + progenitors associated with sinusoids in the bone marrow also indicated more advanced chondrocyte hypertrophic differentiation in SHIP-1 knockout mice than in wild-type mice. In corroboration with the in vivo phenotype, SHIP-1 deficient PDGFRα + Sca-1 + osteochondroprogenitor cells exhibited rapid differentiation into hypertrophic chondrocytes under chondrogenic culture conditions in vitro. Furthermore, SHIP-1 deficiency inhibited hypoxia-induced cellular activation of Akt and extracellular-signal-regulated kinase (Erk) and suppressed hypoxia-induced cell proliferation. These results suggest that SHIP-1 is required for hypoxia-induced growth signaling under physiological hypoxia in the bone marrow. In conclusion, the lipid phosphatase SHIP-1 regulates skeletal development by modulating chondrogenesis and the hypoxia response of the osteochondroprogenitors during endochondral bone formation., (© 2019 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.)
- Published
- 2020
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27. Reliability of OMERACT ultrasound elementary lesions in gout: results from a multicenter exercise.
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Cazenave T, Martire V, Reginato AM, Gutierrez M, Waimann CA, Pineda C, Rosa JE, Ruta S, Sedano-Santiago O, Bertoli AM, Audisio M, Hernandez-Diaz C, Ventura-Rios L, Quintero M, De Miguel E, Alvarez-Del-Castillo-Araujo AL, Abril A, Ayala-Ledesma EN, Alarcon-Isidro E, Santiago ML, Pera MA, Urquiola C, Rodriguez Gil G, Saldarriaga Rivera LM, Cefferino C, Benegas M, Diaz Cortes ME, Bravo M, Peiteado D, Estrella NA, Micas RA, Saavedra Muñoz J, Arape Toyo RDC, Gálvez Elkin MS, Spindler WJ, Sandobal C, Marin J, Lima Gomes Ochtrop M, Pavao Ayala R, Catay ER, Py GE, Aguilar GH, Rengel Colina YY, Airoldi CA, Mora-Trujillo CS, Kohan MP, Urioste Eguez LE, Castillo-Gallego C, Diaz-Coto JF, Tate P, Saucedo CM, Vega-Hinojosa O, Troitiño CJ, Marengo MF, Marcaida PM, Monjo Henry I, Muñoz-Louis R, Solano C, Fernandez Castillo FR, Graf CE, Guinsburg M, Santa Cruz MJ, Navarta Ortiz DA, Alva Linares M, and Rosemffet MG
- Subjects
- Cross-Sectional Studies, Humans, Reproducibility of Results, Ultrasonography, Gout diagnostic imaging
- Abstract
The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.
- Published
- 2019
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28. Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout.
- Author
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Bursill D, Taylor WJ, Terkeltaub R, Kuwabara M, Merriman TR, Grainger R, Pineda C, Louthrenoo W, Edwards NL, Andrés M, Vargas-Santos AB, Roddy E, Pascart T, Lin CT, Perez-Ruiz F, Tedeschi SK, Kim SC, Harrold LR, McCarthy G, Kumar N, Chapman PT, Tausche AK, Vazquez-Mellado J, Gutierrez M, da Rocha Castelar-Pinheiro G, Richette P, Pascual E, Fisher MC, Burgos-Vargas R, Robinson PC, Singh JA, Jansen TL, Saag KG, Slot O, Uhlig T, Solomon DH, Keenan RT, Scire CA, Biernat-Kaluza E, Dehlin M, Nuki G, Schlesinger N, Janssen M, Stamp LK, Sivera F, Reginato AM, Jacobsson L, Lioté F, Ea HK, Rosenthal A, Bardin T, Choi HK, Hershfield MS, Czegley C, Choi SJ, and Dalbeth N
- Subjects
- Crystal Arthropathies classification, Gout classification, Humans, Hyperuricemia classification, Uric Acid analysis, Consensus, Crystal Arthropathies diagnosis, Delphi Technique, Gout diagnosis, Hyperuricemia diagnosis
- Abstract
Objective: The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout., Methods: Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting., Results: There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (≥80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used., Conclusion: Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout., (© 2018, American College of Rheumatology.)
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- 2019
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29. Loss of lipid phosphatase SHIP1 promotes macrophage differentiation through suppression of dendritic cell differentiation.
- Author
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So EY, Sun C, Reginato AM, Dubielecka PM, Ouchi T, and Liang OD
- Subjects
- Animals, Cell Differentiation, Humans, Lipids, Mice, Dendritic Cells metabolism, Macrophages metabolism, Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases metabolism
- Abstract
SH2-containing inositol 5'-phosphatase-1 (SHIP1) deficiency in mice results in abnormal myeloid expansion, and proinflammatory conditions in the lung. However, the mechanisms involved in SHIP1-mediated regulation of myeloid differentiation remain unclear. Here we show that SHIP1 is a key regulator of early differentiation for dendritic cells (DCs). We also provide critical evidence to modify the function of SHIP1 in in vitro development of BMDCs using the recent framework of defining DCs. We found that loss of SHIP1 suppresses GM-CSF-induced formation of bone marrow-derived DC (BMDC) colonies, leading to reduced BMDC number in BM cell culture. The number of maturated BMDCs decreased in SHIP1-KO culture, due to reduction of immature BMDCs, suggesting SHIP1 is critical for lineage commitment rather than for maturation from myeloid precursors to DCs. We further showed that F4/80
+ /MHCIIlow BM macrophage-like cells (BMMs) were the main population of SHIP1-KO BM culture. Treatment of wild-type BM culture with 3 α-aminocholestane (3AC), a specific inhibitor for functional activity of SHIP1, caused a similar developmental defect in BMDCs as seen in SHIP1-KO cells, resulting in the absence of BMDC colony, and increased number of BMMs in BM culture. In conclusion, our results suggest that differentiation of BMDCs are markedly impaired under SHIP1 deficient condition, which causes skewed development of myeloid lineage cells manifested as pathological conditions associated with an excess of macrophage population.- Published
- 2019
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30. Recombinant human proteoglycan-4 reduces phagocytosis of urate crystals and downstream nuclear factor kappa B and inflammasome activation and production of cytokines and chemokines in human and murine macrophages.
- Author
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Qadri M, Jay GD, Zhang LX, Wong W, Reginato AM, Sun C, Schmidt TA, and Elsaid KA
- Subjects
- Animals, Anti-Inflammatory Agents metabolism, Anti-Inflammatory Agents pharmacology, Chemokines genetics, Chemokines metabolism, Crystallization, Cytokines genetics, Humans, Hyaluronan Receptors antagonists & inhibitors, Hyaluronan Receptors immunology, Hyaluronan Receptors metabolism, Inflammasomes metabolism, Macrophages immunology, Macrophages metabolism, Mice, Knockout, Proteoglycans genetics, Proteoglycans metabolism, Recombinant Proteins metabolism, Recombinant Proteins pharmacology, THP-1 Cells, Uric Acid chemistry, Uric Acid pharmacokinetics, Cytokines metabolism, Inflammasomes drug effects, Macrophages drug effects, NF-kappa B metabolism, Phagocytosis drug effects, Proteoglycans pharmacology, Uric Acid pharmacology
- Abstract
Background: Gout is an inflammatory arthritis caused by monosodium urate monohydrate (MSU) crystals' joint deposition. MSU phagocytosis by resident macrophages is a key step in gout pathogenesis. MSU phagocytosis triggers nuclear factor kappa B (NFκB) activation and production of cytokines and chemokines. Proteoglycan-4 (PRG4) is a glycoprotein produced by synovial fibroblasts and exerts an anti-inflammatory effect in the joint mediated by its interaction with cell surface receptor CD44. PRG4 also binds and antagonizes TLR2 and TLR4. The objective of this study is to evaluate the efficacy of recombinant human PRG4 (rhPRG4) in suppressing MSU-induced inflammation and mechanical allodynia in vitro and in vivo., Methods: THP-1 macrophages were incubated with MSU crystals ± rhPRG4 or bovine submaxillary mucin (BSM), and crystal phagocytosis, cytokines and chemokines expression and production were determined. NFκB p65 subunit nuclear translocation, NLRP3 induction, caspase-1 activation and conversion of proIL-1β to mature IL-1β were studied. MSU phagocytosis by Prg4
+/+ and Prg4-/- peritoneal macrophages was determined in the absence or presence of rhPRG4, BSM, anti-CD44, anti-TLR2, anti-TLR4 and isotype control antibodies. Rhodamine-labeled rhPRG4 was incubated with murine macrophages and receptor colocalization studies were performed. Lewis rats underwent intra-articular injection of MSU crystals followed by intra-articular treatment with PBS or rhPRG4. Weight bearing and SF myeloperoxidase activities were determined., Results: rhPRG4 reduced MSU crystal phagocytosis at 4 h (p < 0.01) and IL-1β, TNF-α, IL-8 and MCP-1 expression and production at 6 h (p < 0.05). BSM did not alter MSU phagocytosis or IL-1β production in human and murine macrophages. rhPRG4 treatment reduced NFκB nuclear translocation, NLRP3 expression, caspase-1 activation and generation of mature IL-1β (p < 0.05). MSU-stimulated IL-1β production was higher in Prg4-/- macrophages compared to Prg4+/+ macrophages (p < 0.001). rhPRG4, anti-CD44, anti-TLR2 and anti-TLR4 antibody treatments reduced MSU phagocytosis and IL-1β production in murine macrophages (p < 0.05). rhPRG4 preferentially colocalized with CD44 on Prg4-/- peritoneal macrophages compared to TLR2 or TLR4 (p < 0.01). rhPRG4 normalized weight bearing and reduced SF myeloperoxidase activity compared to PBS in vivo., Conclusion: rhPRG4 inhibits MSU crystal phagocytosis and exhibits an anti-inflammatory and anti-nociceptive activity in vitro and in vivo. rhPRG4's anti-inflammatory mechanism may be due to targeting CD44 on macrophages.- Published
- 2018
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31. Identification of calcium pyrophosphate deposition disease (CPPD) by ultrasound: reliability of the OMERACT definitions in an extended set of joints-an international multiobserver study by the OMERACT Calcium Pyrophosphate Deposition Disease Ultrasound Subtask Force.
- Author
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Filippou G, Scirè CA, Adinolfi A, Damjanov NS, Carrara G, Bruyn GAW, Cazenave T, D'Agostino MA, Delle Sedie A, Di Sabatino V, Diaz Cortes ME, Filippucci E, Gandjbakhch F, Gutierrez M, Maccarter DK, Micu M, Möller Parera I, Mouterde G, Mortada MA, Naredo E, Pineda C, Porta F, Reginato AM, Satulu I, Schmidt WA, Serban T, Terslev L, Vlad V, Vreju FA, Zufferey P, Bozios P, Toscano C, Picerno V, and Iagnocco A
- Subjects
- Acromioclavicular Joint diagnostic imaging, Aged, Female, Hip Joint diagnostic imaging, Humans, International Cooperation, Internet, Male, Metacarpophalangeal Joint diagnostic imaging, Middle Aged, Observer Variation, Radiology Information Systems, Reproducibility of Results, Ultrasonography methods, Wrist Joint diagnostic imaging, Chondrocalcinosis diagnostic imaging, Ultrasonography standards
- Abstract
Objectives: To assess the reliability of the OMERACT ultrasound (US) definitions for the identification of calcium pyrophosphate deposition disease (CPPD) at the metacarpal-phalangeal, triangular fibrocartilage of the wrist (TFC), acromioclavicular (AC) and hip joints., Methods: A web-based exercise and subsequent patient-based exercise were carried out. A panel of 30 OMERACT members, participated at the web-based exercise by evaluating twice a set of US images for the presence/absence of CPPD. Afterwards, 19 members of the panel met in Siena, Italy, for the patient-based exercise. During the exercise, all sonographers examined twice eight patients for the presence/absence of CPPD at the same joints. Intraoberserver and interobserver kappa values were calculated for both exercises., Results: The web-based exercise yielded high kappa values both in intraobserver and interobserver evaluation for all sites, while in the patient-based exercise, inter-reader agreement was acceptable for the TFC and the AC. TFC reached high interobserver and intraobserver k values in both exercises, ranging from 0.75 to 0.87 (good to excellent agreement). AC reached moderate kappa values, from 0.51 to 0.85 (moderate to excellent agreement) and can readily be used for US CPPD identification., Conclusions: Based on the results of our exercise, the OMERACT US definitions for the identification of CPPD demonstrated to be reliable when applied to the TFC and AC. Other sites reached good kappa values in the web-based exercise but failed to achieve good reproducibility at the patient-based exercise, meaning the scanning method must be further refined., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
- Published
- 2018
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32. SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity.
- Author
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Zuo C, Wang L, Kamalesh RM, Bowen ME, Moore DC, Dooner MS, Reginato AM, Wu Q, Schorl C, Song Y, Warman ML, Neel BG, Ehrlich MG, and Yang W
- Abstract
Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by Ptpn11 ) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1 , and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, qRT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration., Competing Interests: The authors declare that they have no conflict of interest.
- Published
- 2018
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33. Musculoskeletal ultrasonography has arrived.
- Author
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Cunha JS and Reginato AM
- Subjects
- Arthralgia etiology, Arthritis, Rheumatoid complications, Female, Humans, Middle Aged, Arthralgia diagnostic imaging, Arthritis, Rheumatoid diagnostic imaging, Ultrasonography methods
- Published
- 2018
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34. Endothelial to haematopoietic transition contributes to pulmonary arterial hypertension.
- Author
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Liang OD, So EY, Egan PC, Goldberg LR, Aliotta JM, Wu KQ, Dubielecka PM, Ventetuolo CE, Reginato AM, Quesenberry PJ, and Klinger JR
- Subjects
- AC133 Antigen blood, Animals, Antigens, CD34 metabolism, Case-Control Studies, Core Binding Factor Alpha 2 Subunit blood, Core Binding Factor Alpha 2 Subunit genetics, Core Binding Factor Alpha 2 Subunit metabolism, Disease Models, Animal, Endothelial Progenitor Cells metabolism, Endothelial Progenitor Cells transplantation, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells metabolism, Humans, Hypertension, Pulmonary genetics, Hypertension, Pulmonary metabolism, Hypertension, Pulmonary physiopathology, Leukocyte Common Antigens metabolism, Mice, Transgenic, Phenotype, Proto-Oncogene Proteins c-kit metabolism, Pulmonary Artery metabolism, Pulmonary Artery physiopathology, Arterial Pressure, Cell Lineage, Cell Transdifferentiation, Endothelial Progenitor Cells pathology, Hematopoietic Stem Cells pathology, Hypertension, Pulmonary pathology, Pulmonary Artery pathology
- Abstract
Aims: The pathogenic mechanisms of pulmonary arterial hypertension (PAH) remain unclear, but involve dysfunctional endothelial cells (ECs), dysregulated immunity and inflammation in the lung. We hypothesize that a developmental process called endothelial to haematopoietic transition (EHT) contributes to the pathogenesis of pulmonary hypertension (PH). We sought to determine the role of EHT in mouse models of PH, to characterize specific cell types involved in this process, and to identify potential therapeutic targets to prevent disease progression., Methods and Results: When transgenic mice with fluorescence protein ZsGreen-labelled ECs were treated with Sugen/hypoxia (Su/Hx) combination to induce PH, the percentage of ZsGreen+ haematopoietic cells in the peripheral blood, primarily of myeloid lineage, significantly increased. This occurrence coincided with the depletion of bone marrow (BM) ZsGreen+ c-kit+ CD45- endothelial progenitor cells (EPCs), which could be detected accumulating in the lung upon PH-induction. Quantitative RT-PCR based gene array analysis showed that key transcription factors driving haematopoiesis were expressed in these EPCs. When transplanted into lethally irradiated recipient mice, the BM-derived EPCs exhibited long-term engraftment and haematopoietic differentiation capability, indicating these EPCs are haemogenic in nature. Specific inhibition of the critical haematopoietic transcription factor Runx1 blocked the EHT process in vivo, prevented egress of the BM EPCs and ultimately attenuated PH progression in Su/Hx- as well as in monocrotaline-induced PH in mice. Thus, myeloid-skewed EHT promotes the development of PH and inhibition of this process prevents disease progression in mouse models of PH. Furthermore, high levels of Runx1 expression were found in circulating CD34+ CD133+ EPCs isolated from peripheral blood of patients with PH, supporting the clinical relevance of our proposed mechanism of EHT., Conclusion: EHT contributes to the pathogenesis of PAH. The transcription factor Runx1 may be a novel therapeutic target for the treatment of PAH., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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35. M1 Macrophage-Induced Endothelial-to-Mesenchymal Transition Promotes Infantile Hemangioma Regression.
- Author
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Wu KQ, Muratore CS, So EY, Sun C, Dubielecka PM, Reginato AM, and Liang OD
- Subjects
- Cell Polarity physiology, Cell Proliferation physiology, Endothelial Cells pathology, Hemangioma, Capillary pathology, Humans, Cell Differentiation physiology, Endothelial Cells metabolism, Hemangioma, Capillary metabolism, Macrophages metabolism
- Abstract
Infantile hemangiomas are benign tumors of vascular endothelial cells (ECs), characterized by three distinct stages: proliferating phase, involuting phase, and involuted phase. The mechanisms that trigger involution of hemangioma into fibro-fatty tissue remain unknown. We report a novel mechanism by which M1-polarized macrophages induce endothelial-to-mesenchymal transition (EndMT) and promote hemangioma regression. M1- but not M2-polarized macrophages induced EndMT in ECs. Tumor necrosis factor-α and, to a lesser extent, IL-1β and interferon-γ were the most potent cytokines produced by the M1 macrophages that induce in vitro EndMT. Western blot analysis and gene expression profiling showed that ECs treated with M1 macrophages, tumor necrosis factor-α, or IL-1β decreased the expression of endothelial markers, whereas mesenchymal markers increased concomitantly. Immunohistochemical staining of patient samples revealed that a significant perivascular infiltration of M1, but not M2, macrophages coincides with endothelial expression of the critical EndMT transcription factors Snail/Slug in involuting hemangiomas. Most strikingly, M1 macrophage-treated ECs isolated from patient hemangiomas (HemECs) but not untreated HemECs readily differentiated into adipocytes on adipogenic induction. Thus, in vitro EndMT and adipogenesis of HemECs have, in part, recapitulated the natural history of hemangioma regression. In conclusion, our findings indicate that EndMT induced by M1 macrophages promotes infantile hemangioma regression and may lead to novel therapeutic treatments for this vascular tumor., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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36. Hyperlipidemic microenvironment conditionates damage mechanisms in human chondrocytes by oxidative stress.
- Author
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Medina-Luna D, Santamaría-Olmedo MG, Zamudio-Cuevas Y, Martínez-Flores K, Fernández-Torres J, Martínez-Nava GA, Clavijo-Cornejo D, Hernández-Díaz C, Olivos-Meza A, Gomez-Quiroz LE, Gutiérrez-Ruiz MC, Pineda C, Blanco F, Reginato AM, and López-Reyes A
- Subjects
- Adipokines genetics, Cells, Cultured, Chondrocytes drug effects, Chondrocytes metabolism, Fatty Acids, Nonesterified administration & dosage, Humans, Hydrogen Peroxide metabolism, Hyperlipidemias complications, Hyperlipidemias genetics, Hyperlipidemias metabolism, Inflammation complications, Inflammation genetics, Inflammation metabolism, Obesity complications, Obesity genetics, Obesity metabolism, Osteoarthritis complications, Osteoarthritis genetics, Osteoarthritis metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism, Hyperlipidemias drug therapy, Inflammation drug therapy, Obesity drug therapy, Osteoarthritis drug therapy
- Abstract
Background: Currently, two pathogenic pathways describe the role of obesity in osteoarthritis (OA); one through biomechanical stress, and the other by the contribution of systemic inflammation. The aim of this study was to evaluate the effect of free fatty acids (FFA) in human chondrocytes (HC) expression of proinflammatory factors and reactive oxygen species (ROS)., Methods: HC were exposed to two different concentrations of FFA in order to evaluate the secretion of adipokines through cytokines immunoassays panel, quantify the protein secretion of FFA-treated chondrocytes, and fluorescent cytometry assays were performed to evaluate the reactive oxygen species (ROS) production., Results: HC injury was observed at 48 h of treatment with FFA. In the FFA-treated HC the production of reactive oxygen species such as superoxide radical, hydrogen peroxide
, and the reactive nitrogen species increased significantly in a at the two-dose tested (250 and 500 μM). In addition, we found an increase in the cytokine secretion of IL-6 and chemokine IL-8 in FFA-treated HC in comparison to the untreated HC., Conclusion: In our in vitro model of HC, a hyperlipidemia microenvironment induces an oxidative stress state that enhances the inflammatory process mediated by adipokines secretion in HC.- Published
- 2017
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37. Acute Knee Fracture Diagnosed by Musculoskeletal Ultrasound.
- Author
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Cunha JS and Reginato AM
- Subjects
- Aged, 80 and over, Arthralgia etiology, Diagnosis, Differential, Humans, Male, Point-of-Care Testing, Arthralgia diagnosis, Femoral Fractures complications, Femoral Fractures diagnosis, Intra-Articular Fractures diagnosis, Knee Joint diagnostic imaging, Ultrasonography methods
- Published
- 2017
- Full Text
- View/download PDF
38. Nail Enthesis Ultrasound in Psoriasis and Psoriatic Arthritis: A Report from the 2016 GRAPPA Annual Meeting.
- Author
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Cunha JS, Qureshi AA, and Reginato AM
- Subjects
- Humans, Severity of Illness Index, Arthritis, Psoriatic diagnostic imaging, Enthesopathy diagnostic imaging, Nails diagnostic imaging, Psoriasis diagnostic imaging, Ultrasonography
- Abstract
Musculoskeletal ultrasonography is gaining favor in the evaluation of enthesitis in patients with psoriasis and psoriatic arthritis (PsA). Imaging modalities have shown that the enthesis of the distal interphalangeal joint has a close relationship to the nail itself. Studies have focused on the structure and morphology of nails to determine an association between psoriasis nail changes and the presence or severity of PsA. With the use of higher frequency probes, power Doppler (PD) can determine subclinical inflammation of the area under ultrasound examination. At the 2016 meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), we proposed an ultrasonographic index for the assessment of the nail enthesis to identify the morphologic and PD findings of the nail, with the potential that both rheumatologists and dermatologists can use it to evaluate their patients.
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- 2017
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39. Erratum to: Musculoskeletal manifestations of primary hyperparathyroidism.
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Pappu R, Jabbour SA, Reginato AM, and Reginato AJ
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- 2017
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40. Musculoskeletal manifestations of primary hyperparathyroidism.
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Pappu R, Jabbour SA, Reginato AM, and Reginato AJ
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- Chondrocalcinosis blood, Chondrocalcinosis complications, Chondrocalcinosis diagnosis, Female, Humans, Hyperparathyroidism, Primary diagnosis, Male, Middle Aged, Musculoskeletal Diseases blood, Musculoskeletal Diseases diagnosis, Osteitis Fibrosa Cystica blood, Osteitis Fibrosa Cystica complications, Osteitis Fibrosa Cystica diagnosis, Parathyroid Hormone blood, Rheumatology, Hyperparathyroidism, Primary complications, Musculoskeletal Diseases complications
- Abstract
Primary hyperparathyroidism (PHPT) can be associated with a variety of musculoskeletal complaints, which occasionally can be the leading or presenting manifestation. In this paper, we describe the musculoskeletal manifestations observed in patients with primary hyperparathyroidism. Medical record reviews of a select population of 74 patients with primary hyperparathyroidism are seen in a rheumatology practice. Bone manifestations included back pain in 11 patients (15.2 %), generalized bone pain in 7 patients (9.7 %), rib cage/chest pain in 6 (8.3 %), pseudoclubbing in 3, and a giant cell tumor of the mandible in 2 (2.3 %) patients. Articular manifestations such as chondrocalcinosis with or without apatite deposition disease were seen in 13 (17.7 %), arthralgias in 11 (15.2 %), and non-specific synovitis in 7 (9.7 %). Muscle weakness was observed in six patients (8.3 %) and myalgias in three (4.6 %). Less common manifestations such as Achilles tendon rupture, Jaccoud-like arthropathy, sacral insufficiency fracture, arthritis associated with fever of unknown origin (FUO), meningitis, cervical cord compression, and persistent headache were observed in single patients. Musculoskeletal findings are still a frequent and important presentation in patients with primary hyperparathyroidism seen in rheumatology practice. Some of these manifestations can be quite unusual and may represent diagnostic dilemmas to the practicing rheumatologist and/or endocrinologist.
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- 2016
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41. PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee.
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Rillo O, Riera H, Acosta C, Liendo V, Bolaños J, Monterola L, Nieto E, Arape R, Franco LM, Vera M, Papasidero S, Espinosa R, Esquivel JA, Souto R, Rossi C, Molina JF, Salas J, Ballesteros F, Radrigan F, Guibert M, Reyes G, Chico A, Camacho W, Urioste L, Garcia A, Iraheta I, Gutierrez CE, Aragón R, Duarte M, Gonzalez M, Castañeda O, Angulo J, Coimbra I, Munoz-Louis R, Saenz R, Vallejo C, Briceño J, Acuña RP, De León A, Reginato AM, Möller I, Caballero CV, and Quintero M
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- Consensus, Delphi Technique, Evidence-Based Medicine, Hand, Humans, Osteoarthritis, Hip therapy, Osteoarthritis, Knee therapy, Practice Guidelines as Topic, Osteoarthritis therapy
- Abstract
Objective: The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America., Methods: Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique., Results: Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement., Conclusions: These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.
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- 2016
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42. Is entheses ultrasound reliable? A reading Latin American exercise.
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Ventura-Ríos L, Navarro-Compan V, Aliste M, Linares MA, Areny R, Audisio M, Bertoli AM, Cazenave T, Cerón C, Díaz ME, Gutiérrez M, Hernández C, Navarta DA, Pineda C, Py GE, Reginato AM, Rosa J, Saaibi DL, Sedano O, Solano C, Castillo-Gallego C, Falçao S, and De Miguel E
- Subjects
- Clinical Competence, Humans, Reproducibility of Results, Severity of Illness Index, Ultrasonography, Enthesopathy diagnostic imaging, Spondylarthritis diagnostic imaging
- Abstract
The objective of this study is to evaluate inter-reader entheses ultrasound (US) reliability and the influence of the type of image or degree of sonographer experience on US reliability in patients with spondyloarthritis (SpA). Eighteen Latin American ultrasonographers with different experience took part in an US reading exercise evaluating 60 entheseal images (50 % static images and 50 % videos) from healthy controls and SpA patients. The following sonographic lesions were assessed: structure, thickness, bone proliferation/tendon calcification, erosions, bursitis, and Doppler signal. Another group of three experts with significant experience in entheses US read all images too. Inter-reader reliability among participants and experts was calculated by the Cohen's kappa coefficient. Thresholds for kappa values were <0.2 poor, 0.21-0.4 fair, 0.41-0.6 moderate, 0.61-0.8 good, and 0.81-1 excellent. Furthermore, the results for the expert group were stratified based on the type of image. Kappa correlation coefficients among participants, showed variability depending on the type of lesion, being fair for structure and thickness, moderate for calcifications, erosions, and bursitis, and excellent for Doppler signal. Inter-reader reliability among experts was higher, being moderate for structure and thickness, good for calcifications and bursitis, and excellent for erosions and Doppler. Inter-reader reliability for assessing calcification and structure using static images was significantly higher than for videos. Overall inter-reader reliability for assessing entheses by US in SpA is moderate to excellent for most of the lesions. However, special training seems fundamental to achieve better inter-reader reliability. Moreover, the type of image influenced these results, where evaluation of entheses by videos was more difficult than by static images.
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- 2016
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43. Erratum to: Is entheses ultrasound reliable? A reading Latin American exercise.
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Ventura-Ríos L, Navarro-Compan V, Aliste M, Alva Linares M, Areny R, Audisio M, Bertoli AM, Cazenave T, Cerón C, Díaz ME, Gutiérrez M, Hernández C, Navarta DA, Pineda C, Py GE, Reginato AM, Rosa J, Saaibi DL, Sedano O, Solano C, Castillo-Gallego C, Falçao S, and De Miguel E
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- 2016
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44. Abnormal Mechanical Loading Induces Cartilage Degeneration by Accelerating Meniscus Hypertrophy and Mineralization After ACL Injuries In Vivo.
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Du G, Zhan H, Ding D, Wang S, Wei X, Wei F, Zhang J, Bilgen B, Reginato AM, Fleming BC, Deng J, and Wei L
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- Animals, Anterior Cruciate Ligament metabolism, Anterior Cruciate Ligament Injuries, Calcinosis metabolism, Cartilage, Articular injuries, Female, Guinea Pigs, Hypertrophy, Knee Injuries, Male, Matrix Metalloproteinase 13 metabolism, Tibial Meniscus Injuries, Anterior Cruciate Ligament pathology, Calcinosis pathology, Menisci, Tibial pathology
- Abstract
Background: Although patients with an anterior cruciate ligament (ACL) injury have a high risk of developing posttraumatic osteoarthritis (PTOA), the role of meniscus hypertrophy and mineralization in PTOA after an ACL injury remains unknown., Purpose/hypothesis: The purpose of this study was to determine if menisci respond to abnormal loading and if an ACL injury results in meniscus hypertrophy and calcification. The hypotheses were that (1) abnormal mechanical loading after an ACL injury induces meniscus hypertrophy and mineralization, which correlates to articular cartilage damage in vivo, and (2) abnormal mechanical loading on bovine meniscus explants induces the overexpression of hypertrophic and mineralization markers in vitro., Study Design: Controlled laboratory study., Methods: In vivo guinea pig study (hypothesis 1): Three-month-old male Hartley guinea pigs (n = 9) underwent ACL transection (ACLT) on the right knee; the left knee served as the control. Calcification in the menisci was evaluated by calcein labeling 1 and 5 days before knee harvesting at 5.5 months. Cartilage and meniscus damage and mineralization were quantified by the Osteoarthritis Research Society International score and meniscus grade, respectively. Indian hedgehog (Ihh), matrix metalloproteinase-13 (MMP-13), collagen type X (Col X), progressive ankylosis homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), alkaline phosphatase (ALP), inorganic pyrophosphate (PPi), and inorganic phosphate (Pi) concentrations were evaluated by immunohistochemistry and enzyme-linked immunosorbent assay. In vitro bovine meniscus explant study (hypothesis 2): Bovine meniscus explants were subjected to 25% strain at 0.3 Hz for 1, 2, and 3 hours. Cell viability was determined using live/dead staining. The levels of mRNA expression and protein levels were measured using real-time quantitative reverse transcription polymerase chain reaction and Western blot after 24, 48, and 72 hours in culture. The conditioned medium was collected for sulfated glycosaminoglycan (GAG) release and Pi/PPi assay., Results: In vivo guinea pig study: Meniscus size and area as well as intensity of meniscus calcification were significantly increased in the ACLT group compared with the control group. Both calcified area and intensity were correlated with cartilage damage in the ACLT group (meniscus calcified area: r = 0.925, P < .0001; meniscus calcified intensity: r = 0.944, P < .0001). Ihh, MMP-13, Col X, ANKH, ENPP1, and ALP expression were increased in the ACLT group compared with the control group. The Pi level and Pi/PPi ratio increased by 63% and 42%, respectively, in the ACLT group compared with the control group. In vitro bovine meniscus explant study: Cell death was found in the superficial zone of the bovine meniscus explants after loading for 3 hours. The mRNA expression and protein levels of MMP-13, ANKH, ENPP1, and ALP were up-regulated in all 3-hour loaded samples. The Pi/PPi ratio and sulfated GAG content in the culture medium were increased in the 3-hour loaded group., Conclusion: Meniscus hypertrophy and mineralization correlated to cartilage degeneration after ACL injuries., Clinical Relevance: The study data suggest that the suppression of meniscus hypertrophy and calcification may decrease the risk of PTOA after ACL injuries., (© 2016 The Author(s).)
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- 2016
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45. New Ultrasound Modalities in Rheumatology.
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Gutierrez M, Okano T, Reginato AM, Cazenave T, Ventura-Rios L, Bertolazzi C, and Pineda C
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- Dimensional Measurement Accuracy, Humans, Imaging, Three-Dimensional methods, Inflammation diagnosis, Inventions, Reproducibility of Results, Rheumatic Diseases diagnosis, Rheumatic Diseases physiopathology, Rheumatology methods, Rheumatology trends, Ultrasonography methods
- Abstract
Over the years, ultrasound (US) has accumulated important evidence supporting its relevant role for the assessment of inflammatory processes of different rheumatologic diseases, as well as in the follow-up in assessing the response to different therapeutic approaches. This has been possible because of the increase in training, competency, and knowledge, as well as the rapid progress in the US technologies.Currently, some US machines can be equipped by sophisticated software modalities (i.e., 3-dimensional US, elastosonography, automated cardiovascular software, and fusion imaging) that can augment US traditional role as a safe, fast, and easy-to-perform modality and giving it new life and increased relevance in rheumatology. In this article, we evaluated the US developments, from conventional B-mode to more sophisticated technologies, and their potential clinical impact in the field of rheumatology.Three-dimensional US can improve the accuracy of the assessment of bone erosions and the quantification of power Doppler because of its multiplanar view including coronal, axial and sagital view. Elastosonography is still looking for its role in rheumatology. Preliminary works induce us to consider it as a promise tool for the assessment of tendon pathology and skin of patients with connective tissue disorders. The automated method for the measurement of carotid intima-media thickness permits a rapid and accurate assessment. The preliminary published data showed that it is reliable, and valid compared to the traditional method; they also support the future of rheumatologists as the direct operators in evaluating the cardiovascular risk in daily practice. Fusion imaging increases the diagnostic power of US, displaying simultaneously in the monitor, the US image, and the corresponding computed tomography/magnetic resonance imaging image. However, there are no sufficient data supporting its application in daily rheumatologic practice.
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- 2015
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46. General Applications of Ultrasound in Rheumatology Practice.
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Amorese-O'Connell L, Gutierrez M, and Reginato AM
- Abstract
A growing body of clinical and research studies have demonstrated the utility of ultrasound for providing better diagnostic and treatment decisions in patients with rheumatic diseases., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
- Published
- 2015
47. Management of Psoriasis and Psoriatic Arthritis in a Multidisciplinary Rheumatology/Dermatology Clinic.
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Cunha JS, Qureshi AA, and Reginato AM
- Abstract
Early diagnosis, use of newly developed targeted therapies, and a multispecialty approach are essential for the treatment of patients with psoriasis and psoriatic arthritis., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
- Published
- 2015
48. Osteoarthritis in Latin America: Study of Demographic and Clinical Characteristics in 3040 Patients.
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Reginato AM, Riera H, Vera M, Torres AR, Espinosa R, Esquivel JA, Felipe OJ, Blas JR, Rillo O, Papasidero S, Souto R, Rossi C, Molina JF, Ballesteros F, Radrigan F, Guibert M, Chico A, Gil ML, Camacho W, Urioste L, Garcia AK, Iraheta I, Gutierrez CE, Duarte M, Castañeda O, Coimbra I, Muñoz Louis R, Reveille J, and Quintero M
- Subjects
- Comorbidity, Cross-Sectional Studies, Demography, Female, Humans, Latin America epidemiology, Male, Middle Aged, Severity of Illness Index, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Arthrography statistics & numerical data, Glucosamine therapeutic use, Hypertension epidemiology, Obesity epidemiology, Osteoarthritis diagnosis, Osteoarthritis drug therapy, Osteoarthritis epidemiology, Osteoarthritis physiopathology, Viscosupplements therapeutic use
- Abstract
Background: Latin America is a heterogeneous region made up of different populations, cultures, latitudes, altitudes, and immigrants from different areas and ethnic groups., Objective: The purpose of this study is to describe the clinical and demographic profile of patients with osteoarthritis (OA) evaluated by a selected group of rheumatologists in 13 Latin American countries., Methods: A descriptive, observational, cross-sectional study was conducted in 13 Latin American countries of patients with symptomatic OA. Data were collected over a 3-month period using an ad hoc questionnaire to evaluate the clinical and demographic features of OA seen by rheumatologists., Results: Among the 3040 patients, their average age was 62.5 years, and female-to-male ratio was 4.8:1. Patients with body mass index of greater than 30 kg/m or obesity was found in 38.2%. Approximately 88% had primary OA. Joints with OA were as follows: knee 31.2%, hand 9.5%, hand and knee 22.9%, proximal and distal interphalangeal joints (erosive OA) 6.5%, axial 6.6%, and hip 1.3%. Approximately 88.5% had radiographic severity of grade 2 or 3 on Kellgren-Lawrence scale (0-4). Nonsteroidal anti-inflammatory drugs were the predominant OA treatment included in combinations with glucosamine sulfate/chondroitin and viscosupplementation. Associated comorbidities included hypertension (39%), obesity (36.3%), diabetes mellitus (12%), and without comorbidity (12.7%)., Conclusions: This is 1 of the largest population studies that evaluated the characteristics of OA in 3040 patients evaluated by rheumatologists in 13 Latin American countries. This study provides important data for each Latin American country to develop new health care planning in management of OA.
- Published
- 2015
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49. Molecular basis of oxidative stress in gouty arthropathy.
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Zamudio-Cuevas Y, Hernández-Díaz C, Pineda C, Reginato AM, Cerna-Cortés JF, Ventura-Ríos L, and López-Reyes A
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- Animals, Antioxidants metabolism, Crystallization, Cytokines metabolism, Humans, Hyperuricemia physiopathology, Immunity, Innate, Inflammation, Joints immunology, Reactive Oxygen Species, Uric Acid metabolism, Arthritis, Gouty metabolism, Oxidative Stress
- Abstract
Gout is a disorder of urate metabolism in which persistent high urate levels in the extracellular fluids result in the deposition of monosodium urate (MSU) crystal in joints and periarticular tissues. In recent years, this disease represents an increasingly common health problem, so the pace of investigation in the field has accelerated tremendously. New research advances in the pathogenesis of hyperuricemia and in the understanding of how MSU crystals induce an acute gouty attack have been focused in this review on the processes of inflammation and involvement of the innate immune response; in addition, we discuss new knowledge about the role of the reactive oxygen species in establishing oxidative stress in MSU crystal-induced arthritis.
- Published
- 2015
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50. Ultrasound-guided procedures in rheumatology. What is the evidence?
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Cazenave T, Pineda C, Reginato AM, and Gutierrez M
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- Humans, Rheumatic Diseases diagnosis, Rheumatic Diseases therapy, Ultrasonography, Interventional
- Abstract
Ultrasound (US) is a cost-effective, noninvasive, and accessible imaging modality that clinicians use at the point of care to assess disease activity and therapeutic efficacy in different rheumatic conditions. It can play a relevant role in invasive procedures performed by the rheumatologist, potentially ensuring a higher degree of accuracy. However, US-guided injections are still underused, and the conventional blind injection the most commonly adopted approach. In this article, we analyze the current evidence supporting the use of US-guided procedures, emphasizing comparative studies between conventional and US-guided procedures and their benefits in the daily rheumatological practice.
- Published
- 2015
- Full Text
- View/download PDF
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